Three bisannulation strategies have been used to rapidly construct pentacyclic benzo‐fused pyrrolo[4,3,2‐mn]acridines, similar to several biologically active natural products. The key steps involve Michael substitution of 2,3‐dichloro‐1,4‐naphthoquinone with o‐nitrophenylacetic acid derivatives, followed by domino amino‐Michael substitutions/cyclisations. The most efficient of these syntheses provided a model compound (1) including the ABCD ring‐system of alpkinidine, in just three steps and 55 % overall yield.
Michael additions of o-nitrophenylacetonitrile have been investigated. The adducts are formed diastereoselectively under mild conditions. Higher temperatures result in an unusual annulation involving intramolecular nucleophilic attack of an enolate on the nitro group, giving rise to 2,3,4-trisubstituted quinolines. In contrast, under similar conditions ethyl o-nitrophenylacetic acid reacts with N-methylmaleimide to give an N-hydroxyindole. A possible explanation for the divergent chemistry, and mechanisms for these reactions are proposed.
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